An Investigation on The Use of Colistin in Critically Ill Patients at A Teaching Hospital in Ho Chi Minh City

Abstract

Colistin is reintroduced into therapeutic protocols as one of the last resort antibiotics against multidrug-resistant (MDR) pathogens. In February 2019, the International Consensus Guidelines (ICG 2019) on optimizing the administration of colistin has for the first time stipulated an official recommendation for higher colistin dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) modeling data. This study aimed at assessing the current dosing of colistin at University Medical Center (UMC) of Ho Chi Minh City (HCMC) and to identify rates and risk factors of colistin-induced nephrotoxicity. A cross sectional study was conducted on patients admitted to Intensive Care Unit (ICU), being treated for severe infection with at least 5 days of colistin IV administration from April 2018 to April 2019. KDIGO criteria were used to evaluate nephrotoxicity during treatment. Colistin-resistance was detected in 4 cases during the study period. The majority (n=104, 87.4%) of patients was diagnosed with pneumonia due to mainly Acinetobacter baumannii. Rational dosing according to PK/PD approach, EMA, FDA was observed in 33 cases (27.8%), 39 cases (32,8%), and 44 cases (38,2%), respectively. 85 cases (71,4%) were evaluated as rational dosing in accordance with at least one of the three guidelines. Clinical efficacy was recorded in 59 infected patients (49.6%). Lower average maintenance dose was observed in patients with treatment failure (p = 0.002). KDIGO-defined acute kidney injury (AKI) developed in 70 patients (58,8%). Multivariate analysis showed that concomitant administration of vasopressors (OR = 16.52; 95% CI 5.3750.83; p = 0.001), furosemide (OR = 5.24; 95% CI 1.89–14.55; p = 0.001) and hypoalbuminemia (< 25 g/l) (OR = 6.24; 95% CI 2.17–17.93; p = 0.001) were significantly associated with nephrotoxicity. Consistent with previous studies, due to a very modest clinical cure rate with a high frequency of colistin-induced AKI and the development of colistin-resistant strains, alternative agents such as new beta-lactam/beta-lactamase inhibitor combinations with favourable safety data are strongly preferred for the treatment of carbapenem-resistant infection.